Bottom Line:
The Aβ+ group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the Aβ- group.The Aβ+ group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability.Our findings suggest that early Aβ aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Aβ deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.

Affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI.

ABSTRACT

There is a growing interest in understanding how amyloid-β (Aβ) accumulation in preclinical Alzheimer's disease relates to brain morphometric measures and cognition. Existing investigations in this area have been primarily conducted in older cognitively-normal (CN) individuals. Therefore, not much is known about the associations between Aβ burden, cortical thickness, and cognition in midlife. We examined this question in 109, CN, late-middle-aged adults (mean age=60.72±5.65 years) from the Wisconsin Registry for Alzheimer's Prevention. They underwent Pittsburgh Compound B (PiB) and anatomical magnetic resonance (MR) imaging, and a comprehensive cognitive exam. Blinded visual rating of the PiB scans was used to classify the participants as Aβ+ or Aβ-. Cortical thickness measurements were derived from the MR images. The Aβ+ group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the Aβ- group. The Aβ+ group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability. Our findings suggest that early Aβ aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Aβ deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.

Mentions:
As a secondary analysis, we examined whether local amyloid burden is correlated with colocalized measures of brain structure using Pearson correlations. For this, FreeSurfer was used to extract mean PiB retention values within each of the eight ROIs by coregistering each participant's DVR image to their FreeSurfer-rendered T1 volume, and then using FreeSurfer's automatic cortical parcellation (APARC) + automatic segmentation (ASEG) template as a mask for extracting mean PiB values in the ROIs. Correlations were conducted using bilateral measures obtained by averaging ROI values across hemispheres. Consistent with the group analyses shown in Table 2, we found that higher entorhinal cortex Aβ accumulation was correlated with decreased entorhinal cortical thickness (r (107) = −0.22, P =.020). We also found a significant association between increased amygdala Aβ burden and decreased amygdala volume (r (107) = −0.23, P =.016). Although the remaining correlations were all in the expected negative direction (i.e., higher Aβ being associated with reduced thickness/volume), they failed to meet our threshold for statistical significance (Ps >.1). These results are plotted in Fig. 1.

Mentions:
As a secondary analysis, we examined whether local amyloid burden is correlated with colocalized measures of brain structure using Pearson correlations. For this, FreeSurfer was used to extract mean PiB retention values within each of the eight ROIs by coregistering each participant's DVR image to their FreeSurfer-rendered T1 volume, and then using FreeSurfer's automatic cortical parcellation (APARC) + automatic segmentation (ASEG) template as a mask for extracting mean PiB values in the ROIs. Correlations were conducted using bilateral measures obtained by averaging ROI values across hemispheres. Consistent with the group analyses shown in Table 2, we found that higher entorhinal cortex Aβ accumulation was correlated with decreased entorhinal cortical thickness (r (107) = −0.22, P =.020). We also found a significant association between increased amygdala Aβ burden and decreased amygdala volume (r (107) = −0.23, P =.016). Although the remaining correlations were all in the expected negative direction (i.e., higher Aβ being associated with reduced thickness/volume), they failed to meet our threshold for statistical significance (Ps >.1). These results are plotted in Fig. 1.

Bottom Line:
The Aβ+ group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the Aβ- group.The Aβ+ group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability.Our findings suggest that early Aβ aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Aβ deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.

Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI.

ABSTRACT

There is a growing interest in understanding how amyloid-β (Aβ) accumulation in preclinical Alzheimer's disease relates to brain morphometric measures and cognition. Existing investigations in this area have been primarily conducted in older cognitively-normal (CN) individuals. Therefore, not much is known about the associations between Aβ burden, cortical thickness, and cognition in midlife. We examined this question in 109, CN, late-middle-aged adults (mean age=60.72±5.65 years) from the Wisconsin Registry for Alzheimer's Prevention. They underwent Pittsburgh Compound B (PiB) and anatomical magnetic resonance (MR) imaging, and a comprehensive cognitive exam. Blinded visual rating of the PiB scans was used to classify the participants as Aβ+ or Aβ-. Cortical thickness measurements were derived from the MR images. The Aβ+ group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the Aβ- group. The Aβ+ group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability. Our findings suggest that early Aβ aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Aβ deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.